Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Development of alcohol-related liver and other diseases appears to be modified by host and environmental factors that include diet and nutritional status, exposure to other drugs and toxins, and infection. The relative importance of alcohol toxicity and malnutrition in the induction of fatty liver and cirrhosis, the subject of this report, has been debated. Male rhesus (M mulatta) monkeys were fed purified liquid diets, adequate or marginally deficient in lipotropes (choline, methionine, and folate), containing ethanol to supply 40-50% of calories for 1.5-4.5 years. Controls, fed the diets with sucrose and fat isocalorically substituted for ethanol, grew well and were clinically normal. Ethanol-fed monkeys in both diet groups failed to gain weight and were slightly anemic, with mild derangements of serum electrolytes and small amounts of fat in their livers. None had fibrosis or cirrhosis until the severity of the lipotrope-deficiency was increased; then two of four deficient animals developed cirrhosis and one developed fibrosis. (The severe deficiency induced weight loss and fatty liver, but not fibrosis, in one of two controls.) We conclude that alcohol does not induce hepatic fibrosis or cirrhosis in rhesus monkeys fed a nutritionally complete diet, a result supported by studies in rats and another monkey, M radiata. Alcohol does induce cirrhosis when fed in combination with a lipotrope-deficient diet that is not, by itself, cirrhogenic.
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PMID:Ethanol and diet interactions in male rhesus monkeys. 692 13

Vitamin A and zinc metabolism are affected both by ethanol and by hepatic cirrhosis. Ethanol causes abnormal dark adaptation by acting as a competitive inhibitor with retinol for alcohol dehydrogenase in the eye. In animals oral ethanol intake results in increased losses of zinc by the urinary and fecal routes. Vitamin A malnutrition in cirrhotics may be caused by poor diet, malabsorption, decreased hepatic vitamin A uptake, and decreased hepatic storage capacity for vitamin A. In some cirrhotic patients zinc deficiency and or protein deficiency may limit the ability to respond to vitamin A. Combined vitamin A and zinc deficiencies are common in cirrhotics and either may result in abnormal dark adaptation or impaired taste and smell. The interaction of these two micro-nutrients must be kept in mind by the clinician caring for alcoholic or alcoholic cirrhotic patients.
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PMID:Vitamin A and zinc metabolism in alcoholism. 700 92

Ethanol has been demonstrated to cause aberrations in lipoprotein metabolism, cholesterol synthesis, biliary secretion, and bile acid synthesis. Although there is interdependency of cholesterol and bile acid metabolism, a role of ethanol-induced lipid abnormalities in altering bile acid synthesis has not been found. The direct effects of ethanol administration on bile acid metabolism have been studied in animals and vary with the experimental design. Acutely, ethanol causes decreased bile acid secretion and synthesis, but other effects are less well defined. Chronic ethanol use in man may result in cirrhosis, a condition in which abnormalities of bile acid metabolism have been described in detail. Cholic acid synthesis and pool size are markedly depressed in advanced cirrhosis. Chenodeoxycholic acid synthesis is affected less than cholic acid synthesis, probably because 12 alpha-hydroxylase activity is markedly depressed in cirrhosis, although other steps may also be influenced such as 7 alpha-hydroxylation of cholesterol or availability of cholesterol precursor. The deoxycholic acid pool is depressed probably because of changes in fecal flora. Despite the decrease in total bile acid pool, lithogenicity of bile is not increased in cirrhotic patients because of a concomitant decline in cholesterol and phospholipid secretion. Changes in hepatic blood flow and hepatic extraction cause an increase in plasma bile acid levels which may have clinical relevance.
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PMID:Effects of acute and chronic ethanol intake on bile acid metabolism. 701 54

Though some epidemiological investigations support the association between pigment gallstone formation and chronic alcoholism with cirrhosis, little attention has been paid to the influence of alcohol itself on biliary bilirubin secretion, so that the pathogenesis of pigment cholelithiasis in alcoholics is hitherto unknown. On different days we intravenously administered ethanol (0.7 g/kg body weight), diluted with 500 ml of saline, or saline alone to 6 non-obese patients with an indwelling T tube and reestablished enterohepatic bile circulation. At the time of the investigation bile cultures were negative for aerobic and anaerobic bacteria. Ethanol significantly increased biliary unconjugated bilirubin in respect to control values. The phenomenon reached a maximum 2 h after alcohol infusion when the value of unconjugated bilirubin averaged 2.37 +/- 0.30% of total bilirubin in contrast to 0.65 +/- 0.14% in control conditions (p less than 0.01), and subsided 6 h after the end of ethanol infusion. Since increased amounts of biliary unconjugated bilirubin predispose to pigment stone formation, it can be speculated that alcohol contributes to pigment cholelithiasis pathogenesis by enhancing the biliary concentrations of this form of pigment.
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PMID:Effect of ethanol on biliary unconjugated bilirubin and its implication in pigment gallstone pathogenesis in humans. 712 55

Ethanol is easily absorbed from the intestine and diffuses quickly throughout body water. The bulk of ethanol is metabolized in the liver, where alcohol dehydrogenase, a complex mixture of isoenzymes, oxidizes ethanol to acetaldehyde. Ethanol abuse produces functional and structural changes in the gastrointestinal tract, such as in the stomach, small intestine, liver, and pancreas. Accumulating evidence suggests direct toxicity of ethanol and possibly of acetaldehyde. Fatty liver, alcoholic hepatitis, liver cirrhosis, acute and chronic gastritis, deranged structure and function of the small intestine, acute and chronic pancreatitis, and pancreatic lithiasis are some of the sequelae of ethanol abuse. Recent investigations have enhanced our understanding of the functional and structural changes of the gastrointestinal tract produced by the abuse of ethanol.
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PMID:Ethanol, the liver, and the gastrointestinal tract. 719 92

To clarify contributions of alcoholic liver injury, dietary fat and acute ethanol intake to alcoholic hypertriglyceridemia, control subjects and alcoholics with fatty liver or cirrhosis were given a high fat meal with and without ethanol. The triglyceridemic response to the meal in patients with fatty liver (551.3 +/- 98.4 mg x hr/dl) was enhanced compared to controls (106.4 +/- 30.9) and characterized by increased fasting and postprandial pre-beta lipoproteins. The cirrhotics' response (262.5 +/- 34.9) was characterized by minimal fasting and postprandial pre-beta lipoproteins and increased postmeal chylomicrons. Ethanol added to the meal enhanced the lipemic response of controls, barely altered the response of patients with fatty liver, and decreased the response of cirrhotics. In an expanded group of alcoholic patients, the percentage of pre-beta lipoproteins determined by electrophoresis reflected the degree of liver injury. Therefore, major determinants of alcoholic triglyceridemia are stage of liver injury and dietary lipid; electrophoretic determination of pre-beta lipoproteins may indicate degree of alcoholic liver damage.
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PMID:Relationship of alcoholic hypertriglyceridemia to stage of liver disease and dietary lipid. 735 47

Following the pioneer report of Di Luzio (Physiologist 6, 169-173, 1963) concerning the prevention of the acute ethanol-induced fatty liver by antioxidants, many observations have shown that ethanol-induced liver injury may be linked, at least partly, to an oxidative stress resulting from increased free radical production and/or decreased antioxidant defence. The disturbances induced in the major hepatic enzymatic and non-enzymatic antioxidant systems following experimental acute and chronic ethanol administration are reviewed, emphasizing the important role of dietary alpha-tocopherol in modifying the induction of oxidative stress and its usual expression as increased lipid peroxidation. Adaptative increases in some elements of the hepatic antioxidant defence partly counteract the enhanced generation of prooxidant free radicals following chronic ethanol intake. By contrast, lipid peroxidation is favoured when ethanol is administered together with a fat-rich diet and/or various xenobiotics. Chronic ethanol feeding has also been reported to potentiate the oxidative stress resulting from an acute ethanol load. By generating potent chemoattractants for human neutrophils and/or by stimulating the expression of genes involved in collagen biosynthesis, liver lipid peroxidation may play an important role in the progression of steatosis to hepatitis and cirrhosis. Oxidative stress has been shown not to be restricted to the liver, but also to affect, under some experimental conditions of ethanol administration, extrahepatic tissues, such as the central nervous system, the heart and the testes. This stress can be partly prevented by vitamin E supplementation. Ethanol-induced antioxidant disturbances have also been reported in clinical studies in blood and liver biopsies. Pharmacological antioxidants could have beneficial effects in reducing the incidence of ethanol-induced changes in cellular lipids, proteins and nucleic acids. The antioxidants considered could act by reducing free radical production (e.g. chelators of redox-active iron derivatives), trapping free radicals themselves, interrupting the peroxidation process or reinforcing the natural antioxidant defence.
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PMID:Alcohol and antioxidant systems. 781 35

Alcohol causes primary malnutrition by displacing nutrients in the diet and secondary malnutrition via malabsorption and cellular injury through direct cytotoxicity. Hepatotoxicity results from metabolic disturbances associated with the oxidation of ethanol via liver alcohol dehydrogenase (ADH) and the redox changes produced by the generated NADH (the reduced form of nicotinamide adenine dinucleotide), which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Ethanol is also oxidized in liver microsomes by an ethanol-inducible cytochrome P450, which contributes to the alcoholic's tolerance and his increased vulnerability to the toxicity of industrial solvents, anesthetics, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and retinoids. Increased acetaldehyde generation, with formation of protein adducts, results in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. Therapy may eventually improve with the use of supernutrients such as S-adenosyl-L-methionine, which replenishes glutathione, restores methylation, and attenuates liver injury, as well as dilinoleoylphosphatidylcholine, which prevents cirrhosis.
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PMID:Herman Award Lecture, 1993: a personal perspective on alcohol, nutrition, and the liver. 823 56

The modifying action of experimentally induced chronic liver injury on diethylnitrosamine (DEN) hepatocarcinogenesis was investigated using a minimal treatment protocol. A single dose of DEN (15 mg/kg b.w.) was administered as a carcinogen to 1-day-old Sprague-Dawley rats. From 3 weeks of age rats received repeated intraperitoneal injections of carbon tetrachloride (CCl4), or 10% ethanol or 5% acetaldehyde in the drinking water for 9 weeks. Combinations of CCl4 and ethanol or acetaldehyde were also tested. Morphology, immunohistochemistry for glutathione S-transferase-placental form, and incidence and quantity of preneoplastic lesions of the livers were studied. The chronic CCl4 administration produced complete or incomplete liver cirrhosis and exerted a strong promoting effect on the development of neoplastic nodules. Ethanol alone revealed no cirrhogenous or tumor-promoting effect, but enhanced both actions of CCl4. Acetaldehyde increased only the cirrhogenous effect of CCl4.
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PMID:Effects of carbon tetrachloride, ethanol and acetaldehyde on diethylnitrosamine-induced hepatocarcinogenesis in rats. 833 Feb 98

Alcohol affects the liver through metabolic disturbances associated with its oxidation. Redox changes produced by the hepatic alcohol dehydrogenase pathway affect lipid, carbohydrate and protein metabolism. Ethanol is also oxidized in liver microsomes by the ethanol-inducible cytochrome P4502E1, resulting in ethanol tolerance and selective hepatic perivenular damage. Furthermore, P4502E1 activates various xenobiotics, explaining the increased susceptibility of the heavy drinker to the toxicity of anesthetics, commonly used medications (i.e. isoniazid), analgesics (i.e. acetaminophen), and chemical carcinogens. Induction of microsomal enzymes also contributes to vitamin A depletion, enhances its hepatotoxicity and results in increased acetaldehyde generation from ethanol, with formation of protein adducts, glutathione depletion, free-radical-mediated toxicity, and lipid peroxidation. Chronic ethanol consumption strikingly enhances the number of hepatic collagen-producing activated lipocytes. Both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and activated lipocytes) ethanol and/or its metabolite acetaldehyde increase collagen accumulation and mRNA for collagen. Gender differences are related, in part, to lower gastric ADH activity (with consequent reduction of first pass ethanol metabolism) in young women, decreased hepatic fatty acid binding protein and increased free-fatty acid levels as well as lesser omega-hydroxylation, all of which result in increased vulnerability to ethanol. Elucidation of the biochemical effects of ethanol are now resulting in improved therapy: in baboons, S-adenosyl-L-methionine attenuates the ethanol-induced glutathione depletion and associated mitochondrial lesions, and polyenylphosphatidylcholine opposes the ethanol-induced hepatic phospholipid depletion, the decrease in phosphatidylethanolamine methyltransferase activity and the activation of hepatic lipocytes, with full prevention of ethanol-induced septal fibrosis and cirrhosis; its dilinoleoyl species also increases collagenase activity in lipocytes. The efficacy of this compound in man is now being studied in randomized multicenter clinical trials.
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PMID:Susceptibility to alcohol-related liver injury. 897 51


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